Adjuvant lipopeptide interaction with model membranes.
The cationic lipohexapeptide Pam3Cys-Ser-(Lys)4 is a synthetic model for the triacylated N-terminal part of bacterial lipoproteins, and it is used as an adjuvant and macrophage activator. The amphiphilic lipopeptide was injected below a phosphatidylserine monolayer at the air-water interface. It interacted with the interface, as seen by a decrease in the surface potential (deltaV), and it was inserted in the monolayer, until surface charge neutralization was reached, as seen by the parallel increases of deltaV and of the surface pressure. No insertion occurred above 29 mN/m. The interaction kinetics was sensitive to ionic strength and to the nature of acidic phospholipids and of their acyl chains, but the final equilibrium was independent of these factors. Addition of the lipopeptide to large unilamellar vesicles (LUVs) induced their aggregation, and an exchange of lipids between fluorophor-labelled and non-labelled LUVs. However, no fusion was observed, just as reported for polylysine. The lipopeptide strongly inhibited calcium-induced fusion of PS LUVs, in contrast to the published effect of polylysine. This was probably due to inhibition of calcium fixation on liposomes, since it was observed that the lipopeptide efficiently displaced 45Ca2+ from a PS monolayer. In addition, a phospholipid segregation was observed in SUVs for a few ten micromolar of the lipopeptide.
Gonzalez-Christen
J
J
Institut de Pharmacologie et de Biologie Structurale du CNRS and Université Paul Sabatier, Toulouse, France.
Vergne
I
I
Süssmuth
R
R
Sidobre
S
S
Prats
M
M
Tocanne
J F
JF
Lanéelle
G
G
D008074:Lipoproteins / Q000378:metabolism*; D008081:Liposomes; D008561:Membrane Fusion; D008567:Membranes, Artificial; D009842:Oligopeptides / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D008074:Lipoproteins; D008081:Liposomes; D008567:Membranes, Artificial; D009842:Oligopeptides; D010743:Phospholipids